Filtration Flashcards
What is filtered at the glomerulus of a nephron? How much is filtered per day? How much urine is excreted per day?
Ultra-filtrate = water, ions, and other small molecules
180l/day filtered (every litre filtered ten times)
1.5l/day excreted
What is the difference between osmolality and osmolarity?
OSMOLALITY = solute/kg of solvent
OSMOLARITY = no. of osmoles of solute/litre
Note: functionally the same as 1kg=1l at standard conditions
Therefore, water moves from LOW OSMOLARITY solutions to HIGH OSMOLARITY solutions (low conc. of solutes to high conc.)
Describe what occurs at the glomerulus.
Water, electrolytes, & small molecules forced through by constant filtration pressure in capillaries
Thin afferent arteriole & thick efferent arteriole
Glomerular filtration rate = ~180l/day (decreased GFR indicates reduced kidney function)
Hydrostatic (tubular) & oncotic (glomerular) pressure oppose the hydrostatic pressure of the plasma (glomerular)
Describe what occurs at the proximal convoluted tubule (in general).
Major site for reabsorption by the peritubular capillaries:
- ~60%-70% of water & Na+ (filtrate remains isotonic)
- ~80%-90% of K+
- ~90% of HCO3-
- 100% of glucose & amino acids (normally)
Simple cuboidal epithelium with brush border
Describe what occurs at the loop of Henle.
Further site of reabsorption & creates increased osmolarity gradient by counter-current multiplication
Thin descending/ascending: simple squamous epithelium
- no active transport
- no RBCs
- no brush border
Thick ascending: simple cuboidal epithelium
- no brush border
- active transport
Describe what occurs at the distal convoluted tubule.
Major site of VARIABLE reabsorption of electrolytes and water
- reabsorbs more Na+ & Cl-
- actively secretes H+ (therefore fluid leaving is hypotonic)
- water may/may not follow reabsorption of electrolytes
Simple cuboidal epithelium
- no brush border
- numerous mitochondria
Describe what occurs at the collecting duct.
Passes through high osmolarity environment of medulla
Aquaporins present: water leaves via osmotic gradient (low volume of concentrated urine)
Aquaporins not present: water remains in urine (diuresis)
Simple cuboidal epithelium
- no brush border
- active transport
- large, irregular lumen
How can sodium recovery be controlled? How can water recovery be controlled?
Sodium recovery: renin-angiotensin system (controls ECF volume)
Water recovery: ADH (controls ECF osmolarity)
What is the definition of a renal corpuscle?
Renal bodies + capillary tuft (glomerulus + Bowman’s capsule)
What is the duct of Bellini?
Merged collecting ducts -> central tube where renal pyramids converge -> open into a renal papilla -> open into a renal calyx
What is the structure of the Bowman’s capsule?
Parietal layer: simple squamous epithelium
Visceral layer: podocytes invest the capillary epithelium, forming filtration slits (spaces between podocyte processes)
note: podocytes and capillary bed share a basement membrane
How do blood components move from the capillary tuft into the Bowman’s capsule?
Capillary endothelium: filtrate (water, salts, glucose) moves between cells
Basement membrane: small proteins move through acellular gelatinous layer of collagen/glycoproteins (large proteins repelled by negative charge of glycoproteins)
Podocyte layer: pseudopodia interdigitate to form filtration slits
What are the key differences between cortical and juxtamedullary nephrons?
Cortical nephrons in cortex, juxtamedullary nephrons next to barrier between cortex and medulla
Renal artery and renal vein separate into ascending and descending vasa recta in the juxtamedullary nephrons only
What are the physical forces which filter plasma in the glomerulus?
- Hydrostatic pressure in capillary (regulated)
- Hydrostatic pressure in Bowman’s capsule
- Oncotic pressure difference between the capillary & tubular lumen
How is the glomerular filtration rate maintained (when BP is within physiological limits)?
Myogenic response:
Afferent arterioles have ability to respond to changes in vessel diameter by contracting or relaxing (stretch activated, non-selective cation channels in vascular smooth muscle -> influx of calcium ions)
e.g. increase in blood pressure -> afferent arteriole constriction
increase in afferent resistance -> reduced hydrostatic pressure ->
reduced GFR
Tubular glomerular feedback:
Macula densa cells in the DCT respond to acute changes in the conc. of Na+ & Cl- (indication of tubular flow rate) by releasing chemicals from the juxtaglomerular apparatus
e.g. increase in [salt] -> adenosine released -> vasoconstriction of
afferent arterioles -> reduced GFR
decrease in [salt] -> prostaglandins released -> vasodilatation of
afferent arterioles -> increased GFR
Describe the actions of membrane transporters involved in reabsorption and secretion at the proximal convoluted tubule. What are the synonymous transporters in the rest of the nephron?
REABSORPTION:
Na+-glucose symporter moves glucose against the conc. gradient
Na+-K+-ATPase maintains sodium gradient
SECRETION:
NHE creates H+ gradient
H+ gradient drives secretion of organic ions into the tubule
Na+-K+-ATPase maintains sodium gradient
+ ROMK maintains K+ gradient
Loop of Henle: Na+-K-2Cl- symporter
Early DCT: Na+-Cl- symporter
Late DCT & collecting duct: ENaC
Why does glucose appear in the urine in diabetics?
Glucose conc. in blood exceeds the transport maximum (Tm) so the not all of the glucose is reabsorbed from the urine
(RENAL THRESHOLD REACHED)
Water follows, causing polyuria
What is renal plasma flow?
1 - Ht x renal blood flow = ~605ml/min of plasma
Ht = haematocrit/erythrocyte volume fraction
What is the filtration fraction? How can this be used to calculate the glomerular filtration rate?
Proportion of a substance that is actually filtered = ~20% filtered
Glomerular filtration rate = 20% of renal plasma flow = 0.20 x 605
= 125ml/min
Therefore, 605 - 125 = 480ml not filtered
What is the definition of clearance? How is this calculated?
Volume of plasma from which any substance is completely removed by the kidney in a given amount of time
i.e. completely cleared from the blood, none metabolised, none reabsorbed, none secreted
Therefore, a substance completely cleared from the urine has a clearance rate of 125ml/min
e.g. inulin (insoluble substance completely cleared from the urine; needs to be infused into the blood)
Clearance rate (ml/min) = Conc. of substance in urine x Urine flow rate divided by the conc. of substance in the plasma
How is GFR estimated in patients?
Cockroft-Gault equation (based on patient data; adjusted for age, weight, sex)
Blood test for the conc. of creatinine in the serum
note: overestimates the GFR (creatinine secreted in PCT)
note: dependent on constant level of creatinine in serum and urine despite protein intake (so inaccurate in AKI/rapid muscle atrophy)
What are the components and function of the juxtaglomerular apparatus?
Macula densa (DCT): chemoreceptors release chemicals in response to acute changes in [NaCl] (change in tubular flow rate) in order to change GFR
Lacis cells (extraglomerular mesangial cells): contract in order to constrict the renal afferent and efferent arterioles (change GFR)
Juxtaglomerular cells of afferent arteriole of glomerulus: release renin (increases GFR) (+granular cells act as mechanoreceptors)
What is the relationship between GFR and kidney function?
GFR indicates how quickly a substance is filtered from the blood into the Bowman’s capsule
Therefore GFR indicates how well the kidney is filtering
What are some of the causes of glycosuria?
Untreated diabetes mellitus - [glucose]blood exceeds renal threshold
note: causes increased volume of filtrate (water moves to area of greater osmolarity) —> polyuria
Pregnancy
Newborns - underdeveloped glucose reabsorption
Chronic renal failure
Renal glycosuria - reduced no. of SGLUT1/2 (benign)
Nephrotic syndrome - increased glomerular permeability
Fanconi syndrome - glucose, amino acids, uric acid, phosphate, and bicarbonate not reabsorbed
What are some of the causes of aminoaciduria?
Overflow aminoaciduria - excessive levels of amino acid in blood exceed renal threshold
Renal aminoaciduria:
Generalised:
- Fanconi syndrome
- Juvenile/Acquired: heavy metal poisoning, drugs, renal diseases
Specialised:
- Cystinuria
- Hartnup’s disease (nicotinamide deficiency —> pellagra)
